TUMORS OF SALIVARY GLANDS.pptx

Dr. MD RAIHAN
PATHOLOGY
TUMORS OF SALIVARY
GLANDS

-3 pairs of major salivary glands- Parotid glands,
submandibular glands and sublingual glands.
-Other locations include- lateral margins of
tongue, palate, lips, buccal mucosa.
- Seromucous glands of nasal cavity, larynx and
bronchi are histologically similar to minor
salivary glands.

-The fundamental structure of all salivary glands is the acinar-ductal unit.
-Acini are variably composed of serous or mucous cells or both.
-Ductal unit include- Striated duct
- Intercalated duct
- Excretory duct
- Acini and intercalated ducts are surrounded by myoepithelial cells.
- Preservation of the lobular architecture is an important feature
favouring the diagnosis of a non-neoplastic process over a tumor.

• Cell differentiation results in three basic models of
salivary gland neoplasm.
-1) In one form of differentiation, tumor cell
population results in a dual population that combines
recognizable luminal/glandular cells with
myoepithelial and/or basal cells.
-2) A second pattern results primarily
in luminal/glandular cells that
resembles to some extent normal
duct epithelial and/or acinar cells.
-3) The third process produces tumor
cells resembling normal myoepithelial
and/or basal cells.

CELLS MORPHOLOGY IMMUNOPHENOTYPE
Serous cells Pyramidal with basal nuclei,
abundant basophilic cytoplasm
rich in zymogen granules.
PAS positive
Mucicarmine negative
Mucous cells Cuboidal, to columnar, have
pale, finely vacuolated
cytoplasm containing
sialomucins.
PAS positive
Mucicarmine positive
Luminal cells
of the
intercalated
ducts
Cuboidal, lightly eosinophilic
cytoplasm and centrally
located nuclei
Cytokeratin
CEA (carcinoembryonic
antigen)
EMA (epithelial
membrane antigen)
CELL MORPHOLOGY AND IMMUNOPHENOTYPIC PROFILE

Myoepithelial cells Stellate shaped,
cytoplasmic processes
embracing the acini or
spindle shaped
surrounding the
intercalated ducts
p63
HMW Cytokeratin
(including CK14)
Calponin Myoid
Actin markers
Variably positive for
S100 protein
GFAP
CD10
Maspin
Basal cells Around the ducts,
differ from
myoepithelial cells in
the absence of
myofilaments. Lack of
myoid markers (actin
and calponin)
p63
HMWCK

- Tumors of the salivary glands are :
*most heterogeneous group of tumors.
*greatest diversity of morphologic
features.
- Relatively uncommon.
- The majority of these neoplasms are benign
80% and only 20% are malignant.
- The various types of salivary gland tumors are
best distinguished by their histologic patterns.

1. Benign Epithelial tumors
• Pleomorphic adenoma
• Myoepithelioma
• Basal cell adenoma
• Warthin’s tumor
• Oncocytoma
• Canalicular adenoma
• Sebaceous adenoma
• Lymphadenoma: a) sebaceous
b) non-sebaceous

• Ductal papilloma: a) Inverted ductal papilloma
b) Intraductal papilloma
c) Sialadenoma papilliferum
• Cystadenoma: Soft tissue tumors
• Hemangioma : a) Hematolymphoid tumors
b) Hodgkin’s lymphoma
• Diffuse large B-cell lymphoma: a) secondary tumors
2) Malignant epithelial tumors
• Acinic cell carcinoma
• Mucoepidermoid carcinoma
• Adenoid cystic carcinoma
• Polymorphous low grade adenocarcinoma

• Epithelial myoepithelial carcinoma
• Clear cell carcinoma, NOS
• Basal cell adenocarcinoma
• Sebaceous carcinoma
• Sebaceous lymhadenocarcinoma
• Cystadenocarcinoma
• Low grade cribriform adenocarcinoma
• Mucinous adenocarcinoma
• Oncocytic carcinoma
• Salivary duct carcinoma
• Adenocarcinoma, NOS
• Myoepithelial carcinoma
• Carcinoma ex pleomorphic adenoma

• Carcinosarcoma
• Metastasizing pleomorphic adenoma
• Squamous cell carcinoma
• Small cell carcinoma
• Large cell carcinoma
• Lymphoepithelial carcinoma
• Sialoblastoma

- Uncommon neoplasms.
- 2% -6% of all head and neck neoplasms.
- Global annual incidence varies from 0.4-13.5 cases
per 100000.
- Most salivary gland tumors originate in the parotid
glands (64-80%), malignancy (15-32%).
- 7-11% occur in submandibular glands, malignancy
(37-45%).
- Less than 1% in the sublingual glands, malignancy
(70-90%).
*

- 9-23% in the minor salivary glands.
- Benign tumors account for 63-78% of all salivary gland
neoplasms.
- Most common benign tumor: Pleomorphic adenoma- 53-
77% of all cases occur in parotid glands.
- Warthin’s tumor- 6-14% of all cases.
- Most common malignancy- Mucoepidermoid carcinoma.
- Most common minor salivary gland tumor sites: palate (42-
54%).
- The proportion of malignant tumors varies significantly by
site and is the greatest in sublingual glands, tongue, floor
of mouth and retromolar area.
- Most common among children: mucoepidermoid
carcinoma.

- Viruses- EBV, CMV, Polyoma virus.
- Ionising radiation.
- Increased occupational risks- asbestos, nickel
compounds or silica dust.
- Employment in woodworking, rubber industries and
beauty saloons.
- Lifestyle- Warthin’s tumor showed a strong
association with cigarette smoking.
- Endogenous hormones.

• Most common benign neoplasm of cells with epithelial
(luminal) and myoepithelial (abluminal) differentiation,
accompanied by variable amounts of stroma.
• The diverse morphology results from amalgamation of
cellular and stromal components.
• The coexistence of apparently epithelial and
mesenchymal elements give rise to synonym “mixed
tumor”.
• Affects women more frequently than men, from 4th
decade to 6th decade with a mean age of 45 years; slow
growing and painless swelling.

• Macroscopically, size ranges from few millimeters to
several centimeters; thinly encapsulated and solitary.
Cut surface may be rubbery, fleshy, mucoid or
glistening, depending on the amount of stroma in
tumor.

• Microscopically, pleomorphic adenoma is characterized
by highly variable growth patterns in different areas of
same tumor.
• Basic cellular organisation
-The prototype histologic appearance consists of tubular
structures enveloped by myoepithelial mantles
submerging in a chondromyxoid stroma. Interface in
between is poorly demarcated.
-The myoepithelial mantle radiated centrifugally, forming
sheets, clusters, lattices and isolated cells, where they
appear to “melt” into the sea of stroma they produce.

• Luminal cell component
- Luminal cell component
takes the form of
anastomosing tubules, cysts,
ribbons and solid sheets.
- The cells are columnar,
cuboidal or flat.
- The duct may be empty or
contain colloid-like material,
which is PAS positive,
diastase resistant and
variably mucicarmine
positive.

• Myoepithelial
component
- Myoepithelial cells
appear as cuboidal,
spindle, stellate,
plasmacytoid hyaline,
nondescript epithelioid
and hydropic clear cells.
- The spindle or cuboidal
cells surround the ducts
in a single layer, thick
mantle or radiating
corona.

- Plasmacytoid hyaline cells represent the most distinctive form of
modified myoepithelial cells; they are oval shaped with
homogeneous eosinophilic hyaline cytoplasm.
- Usually arranged in sheets; often with focal areas of non-cohesive
growth. Nucleus is round and eccentrically located.
- Because their occurrence is restricted to pleomorphic adenoma
and myoepithelioma, their identification is of great diagnostic
value, specially in small biopsies.

- Stellate or spindle
myoepithelial cells
occur singly or form
anastomosing strands,
suspended in
abundant myxoid
matrix.

• Stroma
- Extracellular stroma is one of
the defining features of
pleomorphic adenoma,
although its quantity can range
from scanty to abundant.
- It is composed mostly of acidic
mucosubstances produced by
modified myoepithelial cells
and is positive for Alcian blue,
but variably positive for PAS.
- It takes the form of a mixture
of chondroid (hyaline
cartilage), myxoid,
chondromyxoid, hyaline and
very rarely, osseous and
adipose tissues.

Cytology:
- Fibrillary chondromyxoid ground
substance.
- Variable cellularity of single cells
and poorly cohesive clusters and
sheets.
- Mainly myoepithelial cells, ovoid,
plasmacytoid or spindle, with
abundantly well defined
cytoplasm.
- Regular ovoid nuclei with bland
finely granular nuclear chromatin
and smooth nuclear membrane.
- Spindle shaped myoepithelial cells
embedded in stromal matrix.

A) High power view showing
myoepithelial cells with
abundant pale cytoplasm and
bland nuclei.
B) Fibrillar fibromyxoid stroma
including single oval and
spindle cells

Differential diagnosis:
a) Carcinoma ex-pleomorphic adenoma (Malignant
mixed tumor)- Both may contain PLAG1 or HMGA2
fusion but it demonstrates frank evidence of
malignancy e.g.-marked nuclear pleomorphism, frank
necrosis, invasion beyond pre-existing capsule,
perineural or lymphovascular invasion.
b) Other salivary gland neoplasms- pleomorphic
adenoma may show various architectural and
cytological features that resemble other salivary
gland tumors , identifying areas typical of PA with
triphasic component is helpful to diagnose.
c) Squamous cell carcinoma- both may contain
squamous epithelium with keratinization , but
identification of triphasic components rules out SCC.

• IHC markers:
-Glandular component- EMA, CEA, c-kit.
-Myoepithelial and modified myoepithelial cells are
positive for CK but negative for EMA and CEA.
-Also positive for S100 and GFAP.
-Although CK14 and various myoid
markers (actin, myosin) highlight
normal myoepithelial cells but
pattern of staining in neoplasms
is anarchic. More reliable for
neoplastic myoepithelial cells
are p63 and calponin.

• Represents malignant transformation of a preexisting PA; usually
in setting of a long standing PA or in tumor with multiple
recurrences.
• Incidence ranges from 1.9%-23.3% and risk increses with
duration.
• Malignant transformation is marked by rapid growth after a long
period of minimal increase in size.
• Recurrence and metastasis is common and overall survival is only
30%.
Microscopy
- Malignant component is characterized by widespread significant
cellular pleomorphism, high mitotic count, atypical mitotic
figures, coagulative necrosis and presence of an expansile or
infiltrative nodule within the parent adenoma.

-In most cases, the malignant components dominates the
tumor and is most frequently a high-grade carcinoma
(85% of cases) such as adenocarcinoma NOS or salivary
duct carcinoma; but sometimes adenosquamous
carcinoma, undifferentiated carcinoma, small cell
carcinoma or sarcomatoid carcinoma.

• Cytology :
- A dual population of malignant epithelial cells and benign
cells and stromal components of pleomorphic adenoma.
The epithelial cell cluster in
the right shows prominent
nuclear enlargement and atypia
The cluster on the left is of
benign cells.
Poorly cohesive malignant epithelial
cells In bloody background;
cells at lower left
Appear bland with uniform oval
nuclei.

• Cytogenetics:
Rearrangements of chromosome 8q21 and 12q13-15.
• IHC:
- Overexpression of HER2, S100P, p53.
- Ki67 index is increased (mean 35%)
- Positive for AE1/AE3, CK7, EMA, CEA, vimentin, S100.
- Negative for ER,PR, CK20, desmin, actin, GFAP.

• Carcinosarcoma or, true mixed tumor, is
very rare.
• Mean age at presentation is 62 years,
without sex predilection. Affects major
salivary glands.
• In 1/3rd of cases clinical or histologic
evidence of coexisting pleomorphic
adenoma is present.
• Microscopy – It comprises of frankly
malignant epithelial ( squamous cell
carcinoma or adenocarcinoma) and
mesenchymal (chondrosarcoma,
fibrosarcoma, leiomyosarcoma,
osteosarcoma, liposarcoma,
rhabdomyosarcoma).
• Aggressive tumor with mean survival of
only 29 months.

• Benign cell tumor composed of basaloid cells sharply
delineated from stroma by basement membrane-like
material.
• Typically presents as a solitary ,slow growing ,
otherwise asymptomatic mass. Age at presentation
peaks at 6th-7th decade with a female preponderance.
• 70% occurs in parotid glands and 10-20% in upper lip.
• Rarely undergo malignant transformation (4%) to basal
cell adenocarcinoma, adenoid cystic carcinoma,
salivary duct carcinoma or adenocarcinoma NOS.
• Grossly: well circumscribed solid tumor with
homogeneous, light tan to brown cut surfaces.

• Microscopy:
- Tumor is often surrounded by a fibrous capsule.
- Typically comprises of anastomosing jigsaw puzzle-like islands
and trabeculae, imparting a plexiform appearance.
- The tumor islands and trabeculae are sharply demarcated from
the hyalinized, often highly vascularized stroma by basement
membrane.
- Contains two cell types:
i. Basaloid cells (with basal cell or myoepithelial phenotype)
ii. Luminal cells
Basal cells predominate.
- Scanty cytoplasm and uniform, round or oval, sometimes grooved
nuclei with finely granular chromatin.
- Basal cell adenoma with myoepithelial derived stroma is a
variant with plump spindle cells in the stroma.

Membranous variant:
- Characterized by presence of abundant, thick, eosinophilic
and PAS positive hyaline basal lamina material around the
smooth-contoured basaloid tumor islands.
- Droplets of hyaline material are also found within the
islands.
- Interspersed small glandular
lumens lined by cells with
eosinophilic cytoplasm are
present.

• Cytology :
- Numerous small basaloid cells, both single and
multilayered clusters with occasional peripheral
palisading.
- Scanty cytoplasm, many naked nuclei.
- Regular round or oval nuclei,
may appear dark but with bland,
granular chromatin.
- Scanty fibrous stroma,
hyaline material.

• Low grade malignant neoplasm with cytoarchitectural
resemblance to basal cell adenoma; added with destructive
infiltration of surrounding salivary lobules, nerves or blood
vessels.
• Median age is 60 years, without sex predilection.
• Many arises from preexisting basal cell adenoma, particularly
membranous subtype, or other adenomas, in approximately 23%
of cases.
• Microscopically:
- Predominantly solid growth, characterized by jigsaw puzzle-like
islands of basaloid cells with peripheral palisading.
- Areas with trabecular or membranous arrangement are
frequently present.

- Cases showing nuclear atypia and readily identified
mitotic figures are easy to recognize as being malignant;
but in most cases there is relatively bland cytologic
appearance, and diagnosis is solely based on
identification of infiltrative growth.

• IHC is similar as in basal cell adenoma.

• Benign tumor composed exclusively of neoplastic cells exhibiting
myoepithelial differentiation, without any ductal component.
• Grossly, often thinly encapsulated and has a solid, tan or yellow
cut surface.
• Microscopy:
- The neoplastic myoepithelial cells can be spindled, plasmacytoid
hyaline, epithelioid, clear or oncocytic with the first two cell
types being most common.
- Stroma ranges from being scanty to myxoid, hyaline or sclerotic.
- The spindle cells are elongated with central vesicular nuclei and
eosinophilic cytoplasm; and form variably interlacing fascicles.
- Myoepithelioma consisting predominantly of spindle cells tends to
be more cellular, with little fibrous stroma.

• Pure myoepithelial tumor that demonstrates
cytologic atypia and a potential for aggressive
behaviour; demonstration of infiltrative growth,
cellular atypia, frequent mitosis and coagulative
necrosis.
• Peak age is 6th decade; approximately half of the
cases arise from preexisting pleomorphic adenoma or
myoepithelioma, particularly in recurrences.
• Intermediate to high grade carcinoma.
• Most common site of distant metastasis is lung,
followed by liver and vertebra.
• Grossly, Usually encapsulated and may exhibit areas
of necrosis and cystic degeneration.

• Microscopically,
- The tumor islands exhibit a
cellular periphery and
frequently necrotic or myxoid
central zone.
- Unlike myoepithelioma, it may show one or more of the
following cell types: spindle, epithelioid, plasmacytoid
hyaline and clear cells.
- Nuclear atypia ranges from mild to marked.
- Solid, fascicular, trabecular, festooning and lace-like growth
patterns are common, but glandular structures are not found.

- Variable amounts of hyaline, myxoid or collagenous
stroma are often present.
- Tumors with marked cellular pleomorphism, perineural
invasion, high mitotic count (>61/10 hpf), high Ki67
index (>50%), and p53 protein overexpressionare
associated with worst prognosis.
• IHC: Similar to myoepithelioma.
- Tumor cells commonly express p63,
calponin, S100, CK14, and variably
EMA, CD10, cytokeratin, actin and
GFAP.

• Oncocytoma is a discrete, encapsulated tumor
consisting exclusively of oncocytes and lacking features
of other defined tumor types.
• When accompanied by lymphoid stroma, can simulate
Warthin tumor; and occasionally they may coexist.
• Most commonly occurs in parotid gland of older adults
(mean age 58-77 years) without sex predilection;
submandibular glands can also be affected.
• Radiation in head and neck region has been implicated
in genesis of about 20% of cases.
• Gross: thinly capsulated, mahogany brown, solid
lesion.

• Multifocal nodular oncocytic
hyperplasia is characterized
by multiple nodular
proliferation of closely
packed oncocytes. Features
favourable for diagnosis are:
- Multiple rather than single
nodules
- Lack of capsule
- The nodules usually showing
a lobular configuration
- Frequent clear cell change

• Microscopy:
- Tumor cells form trabeculae, packets, diffuse sheets and
rarely glands, separated by scanty loose vascularized stroma.
- the oncocytes are polygonal or cuboidal, with abundant,
eosinophilic granular cytoplasm, central round nuclei, and
often distinct nucleoli.
- Cytoplasm is packed with mitochondria, which can be
highlighted by PTAH stain or immunostaining with
antimitochondrial antibody.
- Focally sebaceous, goblet cells or squamous differentiation
and psammoma bodies may be present.
- Oncocytoma is prone to infarction either spontaneously or
after fine needle aspiration. Residual viable tumor or
adjacent salivary epithelium commonly undergoes squamous
metaplasia with atypical nuclei, mimicking squamous cell
carcinoma.

• Variant : Clear cell
oncocytoma
- Clear cell are present in
11% of onchocytomas as a
dominant or partial
component.
- The cytoplasmic clearing is
due to glycogen
accumulation, but sparse
granularity is still evident.

• The oncocytic tumor that demostrates malignant
histologic features. Some case may arise from
preexisting oncocytoma.
• Most cases occur in parotid gland of patients aged over
60 years.
• High grade neoplasm with frequent recurrence (56%) and
metastasis (80%), most common to lungs, kidney, liver,
thyroid, mediastinum and bone. Average reported
survival in patients with metastasis is 3.8 years. Tumor
<2cm in diameter has better prognosis.
• Grossly; unencapsulated, single or multinodular tumor.

• Microscopic :
- The oncocytic cells show variations in size and shape and
nuclear pleomorphism, although atypia maybe minimal in
some cases.
- They form trabeculae, sheets, nests or ducts that infiltrate
the salivary gland parenchyma and surround connective tissue.
- Frequent mitotic figures, atypical mitoses, perineural and
vascular invasion can be seen.
- Coagulative tumor necrosis appears to be specific for
oncocytic carcinoma verses oncocytoma and may confer
ominous prognosis; it must not be confused with tumor
infarction of oncocytoma.
- Some tumor show borderline atypical features such as,
callular atypia alone, occasional mitotic figures or limited
local invasion. For such tumors, use of designation “oncocytic
neoplasm of uncertain malignant potential” may be
appropriate.

• Occurs more commonly in elderly, with a mean age of 65
years and slight female predilection.
• Primarily an oral lesion . Upper lip is the site of predilection,
which accounts for 74% of the cases, followed by buccal
mucosa (12%), palate and rarely major salivary glands.
• Patient presents with non-ulcerated, painless mass that grows
slowly.
• Gross:
- Composed of bilayered strands of cells that abut and diverge
haphazardly, giving rise to single files, beads, canalicular and
pseusopapillae.
- The epithelial cells that form strands are cuboidal to
columnar, with moderate amount of amphophilic cytoplasm
and regular oval nuclei.

- Stroma is characteristically edematous with many
capillaries and sinusoids; it can be so loose that
tumor strands may appear to be “floating in the
air”.
• IHC:
- There is exclusive luminal cell differentiation with
myoepithelium or basal cell participation.
- Cells are positive for cytokeratin, vimentin, S100
protein and infrequently EMA.
- A distinct pattern of linear GFAP immunoreactivity is
seen at the interface between tumor cells and
connective tissue.

• Also known as adenolymphoma or papillary cystadenoma
lymphomatosum, is composed of bilayered oncocytic and basal
epithelium forming cystic structure, papillae and glands, which
are accompanied by a dense lymphoid stroma.
• 2nd most common salivary gland tumor.
• Almost restricted appearance is seen in the parotid glands and
peri-parotid lymph nodes.
• Commonly presents as doughy or cystic mass in the inferior pole
of parotid. Presents in the 6th-7th decade and is rare below 40
years. A definite male preponderance (26:1) and mostly
smokers.
• Patients can have no symptoms or can have pain, facial
weakness or ipsilateral ear symptoms such as earache, tinnitus
and deafness.

• Sudden painful increase in size associated with acute
pain (known as cystadenoma lymphomatosum
syndrome) has been postulated to be caused by leakage
papillary of fluid into the surrounding tissue and
retrograde infection from the Stenson’s duct.
• Gross:
- Well circumscribed, spherical to ovoid lesion.
- Cut surface often reveal solid tumor interspersed with
cystic spaces containing clear, mucoid, brown or
“caseous” semisolid debris.
- Prior fine needle aspiration commonly results in areas
of hemorrhages , necrosis, fibrosis.

• Microscopic Appearance: -Irregular cystic structure with the
lining epithelium being thrown into papillary folds.
- The epithelium can also show downward extension to form
loosely arranged or closely packed tubular glands.
- Epithelium consists of 2 layers : a luminal layer of oncocytic
columnar cells supported by a discontinuous layer of oncocytic
basal cells.

- The nuclei of luminal cells appear uniform and display
palisading towards the free surface.
- The brightly eosinophilic granular cytoplasm is due to
accumulation of mitochondria.
- A distinct layer of basement membrane separates the
cystic lining from the lymphoid stroma, which consists
of small lymphocytes mixed with some plasma cells,
histiocytes and mast cells. Germinal cantres and
sinusoids can be seen in some cases.
- The epithelial component can undergo metaplastic
change to squamous, mucous or even ciliated cells,
especially in response to inflammation or infarction.

• Cytology:
- Aspiration of mucoid,
murky fluid.
- Background of
amorphous and
granular debris.
- Bland oncocytic cells
in cohesive,
monolayered sheets.
- Many lymphoid cells.

• Sebaceous cells can normally occur in the parotid gland,
submandibular gland and oral minor salivary glands.
• These are very rare neoplasms that are believed to arise
from these sebaceous-differentiated cells.
• It should be noted that different types of salivary gland
tumors can show focal sebaceous differentiation such as
pleomorphic adenoma, Warthin tumor, mucoepidermoid
carcinoma and epithelial-myoepithelial carcinoma.
• Sebaceous adenoma and lymphadenoma : affected
patients are generally in their 6th-7th decade of life with
slight male predilection; asymptomatic, slow-growing
mass; parotid gland is the most common site.

SEBACEOUS ADENOMA
- Encapsulated tumor comprising multiple
incompletely differentiated sebaceous lobules
accompanied by a fibrous stroma.
- Each lobule consists of groups of mature sebaceous
cells surrounded by basaloid cells.
- Sebaceous cells contain multiple small honeycomb
vacuoles of lipid that can be highlighted by oil red O
staining in frozen section.
- Disintegration of mature sebaceous cells can result
in cystic space formation in the lobule.

SEBACEOUS LYMPHADENOMA
- Has a strong resemblance to Warthin tumor.
- Islands of sebaceous lobules, solid nests, trabeculae,
duct-like structure or cysts are intimately mixed
with a dense lymphoid stroma.
- Cells at periphery of cell
nests and tubulo-glandular
structures have a basaloid
appearance.

• Rare, noninvasive epithelial tumor characterized by cystic
proliferation of benign ductal epithelium.
• Occurs equally in major and minor salivary glands. Mean age
is 55 years with female prediliction.
• Asymptomatic slow growing cyst with or without fluctuance.
• Gross: cut surface of the tumor reveal multicystic spaces or
singly large cyst, into which nodular projections maybe seen;
tumor is well circumscribed with or without a fibrous capsule.
• Microscopic appearance:
- Singe or multiple variably sized cysts are separated by dense
fibrous stroma.
- Cysts are lined by attenuated, cuboidal or columnar epithelial
cells , which maybe thrown into papillary folds.

- The nuclei are bland and mitoses are extremely rare.
- Lumens of cysts contain proteinaceous fluid.

• Cystadenocarcinoma or papillary aystadenocarcinoma
represents the malignant counterpart of cystadenoma.
Low grade malignant tumor.
• Majority of patients are aged above 50 years; no sex
predilection.
• About 65% of cases occur in major salivary glands and
rest affects the buccal mucosa, lips and palate;
presenting as slow growing asymptomatic mass.
- The malignant nature of tumor is manifested by
invasion of the surrounding tissue.
- The cysts are lined by small cuboidal, large cuboidal or
columnar cells or a mixture of these cells.

- Cellular atypia is mild to moderate, but nucleoli
are usually prominent.

• Sialadenoma papilliferum, inverted ductal papilloma, and
intraductal papilloma belong to a group of rare benign
salivary tumors that arise from the excretory ducts or
junction between ductal and mucosal epithelium and are
characterized by papillary growth.
• SIALADENOMA PAPPILIFERUM
- The mean age of the patients is 59 years, with a slight male
predilection.
- The tumor forms an exophytic, papillary, or verrucous growth
from the buccal mucosal surface with a broad or
pedunculated base.
- Microscopic appearance- tumor comprises multiple papillary
processes with convoluted clefts and spaces in between.

• INVERTED DUCTAL PAPILLOMA
- This tumor presents as a nodular submucosal mass beneath an
apparently intact surface.
- The proliferation of papillae appears to start from a pit on the
mucosal surface and grows inward into the underlying stroma.
- The epithelial islands are smooth contoured and sharply
demarcated from the adjacent lamina propria.
- This lesion morphologically resembles inverted papilloma of the
sinonasal tract.
• INTRADUCTAL PAPILLOMA
- Intraductal papilloma develops within a deeply situated salivary
duct, often presenting as unicystic dilatation of a duct.
- A single or double layer of cuboidal to columnar cells forms the
epithelial lining that is supported by thin cores of fibrovascular
tissue.

• Mucoepidermoid carcinoma is an invasive malignant
neoplasm that comprises mucus-secreting cells,
epidermoid cells, and intermediate cells in variable
combinations, forming cysts and solid islands.
• This is the most common malignant salivary gland
neoplasm in adults and children.
• The tumor typically presents as a slow-growing painless
mass. About one third of patients have tenderness,
pain, drainage from the ipsilateral ear, dysphagia, and
trismus.
• Age at presentation spans from the first to the ninth
decades, peaking in the 4th decade. A slight female
predilection is seen.

• The parotid gland (45%) and palate (21%) are the most
common sites of occurrence.
• Mucoepidermoid carcinoma is the principal histologic type of
radiation-related salivary gland carcinoma. This tumor also
occurs with increased frequency among children who received
radiotherapy.
• Grossly: Mucoepidermoid carcinoma appears as an ill-defined
mass that may be partially encapsulated, with firm to hard
consistency. Interspersed cysts that contain mucus or blood-
stained fluid can be found.
- Most cases exhibit irregular invasive borders.
- The tumor comprises haphazardly dispersed mucin-filled cysts
and tumor nests composed of mucous, squamoid (epidermoid),
and nondescript intermediate cells in variable combinations

-The stroma is characteristically sclerotic and abundant,
with infiltrates of chronic inflammatory cells and
occasional extravasated mucin pools.

• Low grade mucoepidermoid carcinoma:
- Variably-sized, mucin-filled cystic structures constitute a
significant component of the tumor, and abundant mucous
cells are present.
- Rounded or irregular-shaped solid epithelial islands are almost
always present.
- The tumor cells have bland-looking nuclei, and mitotic figures
are rarely seen.
- Mucous cells are large, columnar, goblet-shaped or polygonal
cells with copious mucin, imparting a frosted glass appearance
to the cytoplasm. The intracellular mucin can readily be
demonstrated by mucicarmine or diastase-PAS stain.
- Another major cell type is the intermediate cell, which is a
small to medium-sized polygonal cell with a nondescript
appearance

• High grade mucoepidermoid carcinoma
- High-grade mucoepidermoid carcinoma shows more
solid areas and few cystic spaces.
- The solid areas are formed by large polygonal squamoid
(epidermoid) cells with pale to eosinophilic cytoplasm
and distinct cell borders.
- Cellular pleomorphism, nuclear hyperchromasia, and
mitotic figures are more impressive, and areas of
coagulative necrosis may be present.
- Mucous cells are usually sparse, such that staining for
mucin may be required to identify them.

• Intermediate grade mucoepidermoid carcinoma
- The intermediate-grade tumors lie histologically between the
low- and high-grade tumors.
- Cystic spaces do not constitute a significant portion of the
tumor.
- Some degree of nuclear pleomorphism is observed in the
tumor cells. Epidermoid features are generally more obvious
than in the low-grade tumors.

• Variants of mucoepidermoid carcinoma
- Large polygonal clear cells with discrete cell membrane,
abundant water-clear cytoplasm,and eccentric nuclei are
a minor component of many mucoepidermoid carcinomas.
- The clear cell variant appears to be more common in the
palate.

- Focal spindle cell growth and
oncocytic change are
uncommon patterns
observed in some
mucoepidermoid
carcinomas.
- Sclerosing mucoepidermoid
carcinoma with eosinophilia

• Cytology:
- Smears usually of low
cellularity, a ‘dirty’ background
of mucous and debris.
- Cohesive clusters and sheets of
epithelial cells and small
streams of cells within mucous.
- Predominantly intermediate
cells resembling squamous
metaplastic cells; infrequently
differentiated squamous
squamous cells.
- Relatively bland nuclei;
prominent nucleoli in some
cells.
* high grade
mucoepidermoid Ca

• IHC:
- The tumor cells are positive for cytokeratin.
- Variable staining for EMA, CEA, and S100 can be seen.
- p63 immunoreactivity is often extensive and is
observed in the intermediate, epidermoid, and clear
cells.The extensive p63 staining can help in distinction
from mimics such as acinic cell carcinoma and
oncocytoma.
- Myoepithelial markers such as actin and calponin are
negative. In contrast to squamous cell carcinoma,
mucoepidermoid carcinoma often expresses
cytokeratin 7.
- Mucoepidermoid carcinomas express a variety of
membrane-bound mucins including MUC1, MUC4,
MUC5AC, and MUC5B.

• Genetics feature:
- Translocation involving CRTC1 (CREB regulated
transcription coactivator-1 and mastermindlike gene
family (MAML2), located at chromosomes 19p13 and
11q21, respectively, is the most frequent genetic
alteration disrupting the Notch signaling pathway.
• Prognostic factors:
- The 5-year overall survival and disease-free survival of
patients with mucoepidermoid carcinoma are 79.3% and
76.5%, respectively.
- Unfavorable prognostic indicators include involved
surgical margins, positive lymph nodes, extracapsular
lymph node spread, vascular invasion, perineural
invasion, aneuploidy, high proliferative index (mitotic
count >2/10 hpf or MIB1 index >10%), and expression of
MUC1.

Differential Diagnosis
1. Warthin tumor with squamous/mucinous metaplasia.
2. Pleomorphic adenoma with squamous
differentiation.
3. Cystadenoma or cystadenocarcinoma.
4. Poorly differentiated adenocarcinoma (vs. highgrade
mucoepidermoid carcinoma).
5. Squamous cell carcinoma.
6. Adenosquamous carcinoma

• Adenoid cystic carcinoma is an invasive neoplasm composed
predominantly of basaloid cells with myoepithelial/ basal cell
differentiation, accompanied by interspersed ductal
structures.
• Adenoid cystic carcinoma most commonly presents in the 4th-
6th decades, with a slight female predominance (3: 2). The
parotid gland, submandibular gland, and palate are most
commonly involved.
• Clinically, the most common complaint is a slowgrowing
swelling.
• Tenderness, pain, and facial nerve palsy may also be present
because of the marked propensity of the tumor for neural
invasion.
• Distant metastasis (most commonly to lung, bone, and soft
tissue) is more common than regional lymph node metastasis.
The long-term prognosis is poor.

• Grossly, the tumor is tan, fleshy, firm, and invasive.
- Infiltrative growth is usually obvious on histologic
examination, and perineural invasion is very common.
- The three characteristic growth patterns (cribriform,
tubular,and solid) are present in variable combinations.
- The stroma is fibrous with variable amounts of
myxohyaline material.
- Cribriform Pattern:
 The cribriform structures are the most characteristic
feature of adenoid cystic carcinoma.
 They are variably-sized, smooth-contoured, discrete to
coalescent islands comprising small, uniform basaloid
cells punctuated by round rigid spaces, giving rise to a
“Swiss cheese” appearance.

 The majority of the spaces are not glandular lumens
but are surrounded by basaloid (basal/myoepithelial)
cells.
 These spaces are filled with eosinophilic hyaline
material (PAS positive, diastase resistant) and/or
lightly basophilic myxoid ground substance (alcian
blue positive).
 The neoplastic basaloid cells constitute the major cell
population. They possess round or angulated nuclei
and scanty cytoplasm with indistinct cell borders.
Some cells may have pale to clear cytoplasm.
 Nuclear pleomorphism is usually mild, and mitotic
figures are usually few or absent.

• Tubular Pattern:
- The elongated tubules are lined
by a single layer of ductal
epithelial cells surrounded by
a single or multiple layers of
basaloid cells.
- This is the architectural pattern in which glandular lumens
are most easily and consistently found. The glandular lumens
areempty or contain secretion.
- The tubules can be apparently coiled on themselves,
producing a necklace appearance. They are often embedded
in abundant hyaline stroma, to the extent that they may
become “strangulated.”

• Solid Pattern:
- The solid pattern is characterized by smooth-contoured or
focally jagged sheets and islands of closely packed basaloid
cells.
- The basaloid cells, in comparison with those seen in the
cribriform and tubular patterns, usually exhibit more
significant nuclear pleomorphism and mitotic activity.
- Few interspersed true glandular lumens are usually seen.

• Dedifferentiated Adenoid Cystic Carcinoma:
- Dedifferentiation of adenoid cystic carcinoma is
associated with bulky disease, frequent local
recurrence and metastasis, and rapidly fatal outcome.
- TP53 gene mutation, HER2
overexpression, cyclin D1
overexpression, and loss of
RB expression have variably
been demonstrated.

• Cytology:
- Cellular smears, cells both
single and clustered.
- Hyaline spherical globules of
varying size with adherent
tumor cells.
- Scanty cytoplasm, high N:C
ratio, nuclear molding, naked
nuclei.
- Relatively uniform, round or
oval hyperchromatic nuclei;
coarse nuclear chromatin;
nucleoli.

• IHC:
- Immunostaining shows that the basaloid cells exhibit
basal/myoepithelial differentiation.
- These cells express cytokeratin, S100 protein ,actin
(variably), calponin, and p63.
- The interspersed ductal epithelial cells express
cytokeratin (strongly), CK7, CEA, EMA, and c-kit (CD117).
- CD43, a marker of T cells and histiocytes, is
preferentially expressed in adenoid cystic carcinomas,
and none other salivary gland tumors.
• Genetic factors: A distinctive chromosomal
translocation, t(6;9)(q2223;p23-24), which results in
MYB-NFIB gene fusion, is found in adenoid cystic
carcinomas, irrespective of the anatomic site (e.g.,
salivary gland, sinonasal tract, trachea, larynx, breast,
and vulva).

• Prognostic factors:
- Advanced clinical stage, extracapsular spread from
lymph nodes, location in minor gland, large tumor
size (>2-4 cm), bone invasion, involved excision
margins, nondiploid DNA content, high S-phase
fraction, and high Ki67 index have been reported to
be poor prognostic factors.
• Differential diagnosis
- Basal cell adenoma
- Pleomorphic adenoma
- Basal cell adenocarcinoma
- Basaloid squamous cell carcinoma

• Acinic cell carcinoma is a neoplasm demonstrating at least
focal differentiation toward serous acinar cells.
• The most frequent sites of occurrence are the parotid
gland (84%) and submandibular gland (4%).
• It is the most common malignant tumor that may present
bilaterally (3%). A slight female predominance is observed,
and the mean age at presentation is 44 years.
• Acinic cell carcinoma typically presents as a slowgrowing
mass with or without pain.
• Local recurrence and metastasis are often delayed,
sometimes for more than 30 years after the initial
presentation.

• Grossly: Acinic cell carcinoma is often circumscribed
with an incomplete capsule, but it can be multinodular
or infiltrative. The cut surface is solid with or without
cystic areas.
- The tumor is compactly cellular with little sclerotic
stroma except for occasional traversing fibrous bands.
- Lymphoid aggregates, with or without lymphoid follicle
formation, can be present.
- In general, the nuclei are bland looking, and mitotic
figures are rare.
- In contrast to normal acinar cells, these cells are
polygonal instead of triangular, there is greater
variability in size with nuclear hyperchromasia, and
they frequently show a range of granularity

- The tumor cells are most commonly arranged in organoid
sheets traversed by ramifying delicate blood vessels,
sheets punctuated by microcystic spaces, cords,
intertwining solid or near-solid tubules, and coalescent
acini.

- Some cells can exhibit a
reticulated or foamy quality
in the cytoplasm.
• Papillary cystic variant:
- Rare variant is characterized by large cystic spaces
lined by simple or stratified cuboidal epithelium with
some papillary projections.

• Follicular variant
• Dedifferentiated Acinic Cell Carcinoma

• Cytology:
- Abundant cell material
with a clean background.
- Cells mainly in clusters,
scanty inconspicuous
fibrovascular stroma.
- Abundant, fragile, finely
vacuolated, occasionally
dense oncocyte like
cytoplasm.
- Rouned, medium sized
nuclei, mild to moderate
anisokaryosis, bland
chromatin. Many striped
nuclei.

• IHC:
-Most tumor cells exhibit immunohistochemical evidence of
differentiation toward acinar cells or ductal cells, such as
positivity for cytokeratin (especially low molecular weight
cytokeratin), CEA, and amylase.
• Prognostic markers: The most important prognostic
indicators are clinical stage and resection margin status.

• Malignant tumor characterized by infiltrative growth,
morphologic diversity, and cytologic uniformity.
• Occurs almost exclusively in the minor salivary glands.
• The peak age of presentation is in the fifth and sixth
decades, but children can also be affected.
• PLGA is a low-grade neoplasm, with 95% survival rate.
• Grossly, most tumors are circumscribed but
nonencapsulated, with a light tan to gray glistening cut
surface.
- The three most common patterns are tubular, trabecular, and
solid nests. Variability of the growth pattern is the most
consistent feature of the tumor.

• IHC:
- The tumor cells show immunoreactivity for
cytokeratin, EMA, and S100 protein.
- Overexpression of BCL2 protein has been demonstrated
consistently in PLGA.

• Epithelial-myoepithelial carcinoma is a malignant
tumor composed of ductal structures lined by a single
layer of ductal cells that are surrounded by a single or
multiple layers of clear myoepithelial cells. Low grade
malignancy.
• The peak incidence is in the 6th-7th decades (mean age
61 years), with a slight female predominance.
• Approximately 60% of cases occur within the parotid
gland, whereas submandibular gland, sinonasal tract,
and palate are responsible for the rest.
• Most patients present with an asymptomatic mass.

• Grossly, the tumor is typically multinodular and
circumscribed. The cut surface is tan colored and firm.
• the tumor invades the surrounding parenchyma in broad
fronts, resulting in multiple tumor nodules separated by
sclerotic stroma.
• The prototypic bicellular architecture consists of a tubular
structure lined by ductal cells surrounded by one or several
layers of abluminal cells, which are further enveloped on the
outside by a well-defined basement membrane.
• The tubular luminal cells are cuboidal, with round, bland-
looking nuclei and a moderate amount of pink cytoplasm.
• In most cases, cytologic atypia is mild, and the mitotic
count is low.

- The abluminal cells are polygonal, are considerably
larger in size, and often have abundant water-clear
cytoplasm because of accumulation of glycogen.
- The abluminal cells can exhibit “ancient change,” with
occasional nuclei have enlarged hyperchromatic nuclei.
Epithelial-myoepithelial carcinoma. A, The basic neoplastic unit comprises discrete tubules lined by
an inner layer of ductal cells with eosinophilic cytoplasm and an outer layer of large clear
myoepithelial cells. The tubules are separated by hyalinized stroma. B, The tubules can be
surrounded by thicker mantles of clear cells, which coalesce to form larger cellular islands.

• The double-clear variant is characterized by clear cell
change not only in the abluminal myoepithelial cells
but also in the luminal cells. When the epithelial
component shows proliferation to form solid or
cribriform architecture, it can be difficult to
distinguish between the luminal and myoepithelial cells
on morphologic grounds.

• Cytology:
- Cells in tissue fragments, clusters and single.
- hyaline stromal globules may be present.
- A distinct biphasic population is seen only in some cases.
- Myoepithelial (clear) cells less cohesive with pale, fragile
cytoplasm, moderate nuclear enlargement and atypia; naked
nuclei common.
- Epithelial cells are smaller, uniform and in tight clusters.

• Two types of progression is seen. The first is progression to
higher grade epithelial-myoepithelial carcinoma,
characterized by more solid growth, a greater degree of
nuclear atypia, and frequent mitoses. The prognosis is
worsened.
• The second is dedifferentiation (high-grade transformation)
to a high-grade carcinoma lacking evidence of myoepithelial
differentiation. The prognosis is greatly worsened.
• IHC:
- The ductal cells are strongly positive for pan-cytokeratin and
variably positive for S100 protein but are negative for
myoepithelial markers.
- The abluminal cells are positive for pan-cytokeratin (often
weakly), and markers of myoepithelium are easy to
demonstrate, such as p63, S100 protein, calponin, and actin .

• Salivary duct carcinoma is an aggressive malignant
tumor.
• Salivary duct carcinoma most frequently affects the
elderly (peak incidence at 6th-7th decade ), with a
male to female ratio of 3 to 6 : 1. The parotid gland
accounts for 80% of cases.
• The patients commonly present with a rapidly
enlarging parotid mass associated with facial nerve
palsy (42%), pain (23%), and cervical lymphadenopathy
(35%).
• This is one of the most aggressive salivary gland
carcinomas. The tumor mortality can be as high as 77%.
•

• Grossly, The tumor is poorly circumscribed, predominantly
solid, and tan colored. Foci of necrosis are often present.
Gross extension of tumor beyond the salivary gland is
noted in about 70% of cases.
-The infiltrative tumor resembles mammary intraductal
carcinoma and invasive ductal carcinoma.
-The intraductal like component
shows cribriform, papillary-cystic,
or solid patterns, often with
prominent comedo necrosis.

• However, most of them are not genuine intraductal
proliferations because a myoepithelial layer is lacking,
and similar structures can be seen in metastatic
deposits.
• The obviously infiltrative component consists of cords,
nests, small glands, and single cells.
• The neoplastic cells in both components have a similar
apocrine appearance, with abundant eosinophilic
cytoplasm, large pleomorphic vesicular nuclei, and
prominent nucleoli.
• Vascular invasion, perineural invasion, intravascular
tumor emboli, and invasion of adjacent structures are
common.

• Several histologic variants of salivary duct carcinoma
have been described.
-Sarcomatoid Variant (Dedifferentiated Salivary Duct
Carcinoma).
 Comprises anaplastic spindle cells, bizarre
multinucleate giant cells, rhabdoid cells, and, rarely,
osteosarcomatous cells.
The conventional salivary
duct carcinoma component is
seen in the left upper field.
The sarcomatous component
is formed by spindle and
stellate cells with
pleomorphic nuclei.

- Mucin-Rich Variant:
 Areas of mucinous/colloid carcinoma in which clusters of
carcinoma cells with or without cytoplasmic mucin float in
mucin pools.
- Invasive Micropapillary Variant:
 This variant is characterized by
morule-like tumor cell clusters
without fibrovascular cores,
surrounded by clear space. Most
aggressive histologically.
- Oncocytic Variant:
This variant features oncocytic changes
in some areas of the tumor, mimicking oncocytic carcinoma.
The tumor cells have abundant eosinophilic granular cytoplasm
and are strongly immunoreactive with antimitochondrial
antibody.

• IHC:
-The neoplastic cells show diffuse strong staining for
cytokeratin, EMA, and CEA.
- Ki67 index is high (mean 21.3%).
- A proportion of cases overexpress HER2 or epidermal
growth factor receptor (EGFR), and the former finding is
associated with a worse prognosis.
• Genetic features:
-Mutations and overexpression of TP53 gene and protein
are frequent.
- Deletion of the PTEN tumor suppressor gene occurs in
67% of cases.
- HER2 gene amplification occurs in 12% to 36% and
protein overexpression in 26% to 100%.

• a/k/a Low-Grade Salivary Duct Carcinoma or Low-
Grade Cribriform Cystadenocarcinoma.
• It is characterized by pure intraductal proliferation of
tumor cells and probably represents the precursor of
salivary duct carcinoma.
• Most frequently affects the parotid gland of the
elderly, with a slight female predilection. Minor
salivary glands can also be affected.
• The outcome is excellent after complete excision,
with no metastasis or mortality at follow-up of 2 to 12
years.

- Multiple smooth contoured ducts with epithelial cell
proliferation forming cribriform, fenestrated, solid-comedo,
micropapillary, or Roman-bridge patterns.
- The constituent cells show low, intermediate, or high-grade
cytologic atypia.
- The stroma is sclerotic and may exhibit secondary changes
such as hemorrhage, chronic inflammatory infiltrate, and
dystrophic calcification.
- A diagnosis of intraductal carcinoma can be confidently made
only when an invasive component has been ruled out after
complete sampling. It is also imperative to perform
immunostaining to demonstrate an intact myoepithelial layer
around each tumor island .
- IHC: The neoplastic cells variably express androgen receptor,
HER2, and GCDFP-15 (BRST-2), and some cases show HER2
gene amplification.

• Clear cell carcinoma NOS, also known as clear cell
adenocarcinoma, is composed of monomorphic
epithelial cells with water-clear cytoplasm without
evidence of myoepithelial differentiation.
• It is a diagnosis of exclusion, in that features
characteristic of other neoplasms (most notably
epithelial-myoepithelial carcinoma, clear cell
oncocytoma, mucoepidermoid carcinoma, acinic cell
carcinoma, clear cell myoepithelial tumor, sebaceous
carcinoma, and metastatic renal cell carcinoma)
should be absent.
• Most frequently occurs in the fifth to seventh
decades, with no sex predilection.

• Most reported cases arise from the minor salivary glands of the
oral cavity as a painless slow-growing mass.
• It is a low-grade, locally invasive tumor, with a tendency for
locoregional recurrence.
• Cervical lymph node metastasis only rarely occurs, and
mortality due to this tumor is exceptional.
• Grossly, The tumor is poorly circumscribed and shows whitish
tan cut surfaces.
• Microscopically:
- It is composed of sheets, streaming columns, nests, and cords
of large, monomorphic clear cells that show mild variation in
size.
- The cells possess discrete cell membranes and abundant clear
cytoplasm because of accumulation of glycogen (PAS positive
and diastase sensitive, mucicarmine negative).
- The nuclei are centrally or eccentrically located and have
finely granular chromatin and inconspicuous nucleoli. Nuclear
atypia ranges from mild to moderate.

• IHC:
- Immunoreactive for cytokeratin.
- In contrast to metastatic renal cell carcinoma, the tumor
expresses high molecular weight cytokeratin and CEA.
- Myoepithelial markers should be negative.
• Variant: Hyalinizing Clear Cell Carcinoma
- The infiltrative tumor comprises uniform clear cells and cells
with eosinophilic cytoplasm, forming solid nests, trabeculae,
cords, and streaming columns of one to two cell widths.
- The stroma is characterized by abundant, thick parallel
strands of fibrous tissue.
- diffuse positivity of tumor cells for cytokeratin and EMA and
focal positivity for CEA.
- EWR1-ATF1 gene fusion (which is also a molecular hallmark
of clear cell sarcoma of soft tissues and angiomatoid fibrous
histiocytoma) is found in most cases.

• Undifferentiated carcinomas of the salivary glands are
uncommon high-grade malignant tumors.
• Generally, these tumors are classified into small cell and
large cell types. Lymphoepithelial carcinoma is a specific
subtype with a relatively favorable prognosis.
• Small Cell Carcinoma:
- Malignant tumor characterized by small epithelial cells (<30
µm) with scant cytoplasm, fine chromatin, and
inconspicuous nucleoli.
- On the basis of ultrastructural and immunohistochemical
features, it can be categorized into the following:
 1. Neuroendocrine type a. Merkel cell subtype b. Pulmonary
subtype
 2. Ductal type (extremely rare)

• Patients range in age from the 5th-7th decades (mean
54-56 years), with male predilection.
• The tumor manifests as a fast-growing mass with or
without concomitant cervical lymphadenopathy. Facial
nerve palsy is noted in 60% of patients.
• An aggressive malignancy, with local recurrence and
distant metastasis rates over 50%. The overall survival
rate is 40% to 50%.
• A better prognosis has been found to be associated
with Merkel cell subtype, small tumor size (<3-4 cm),
and expression of more neuroendocrine markers.
• Grossly, the tumor is a widely infiltrative mass with
firm consistency and white to yellow color.

-The tumor grows in a diffuse or cord-like pattern and is
traversed by delicate fibrovascular septa.
-The tumor cells are slightly larger than lymphocytes,
with finely stippled chromatin and inconspicuous
nucleoli.
-The nuclei are susceptible to crushing artifact resulting
in deformation and clumping of nuclei, as well as
diffusion of chromatin material.
- Necrosis is commonly seen.
-Vascular and perineural invasion are common.
-In the Merkel cell subtype, the nuclei tend to be round,
nonmolded, resembling blown-up balloons, with pale
and “washed-out” chromatin.

- In the pulmonary subtype, tumor cells are often short and
spindled with nuclear molding, and pseudorosette
formation can be seen.
- However, the morphologic features of these two subtypes
overlap, and the distinction may not be made with
certainty on histologic examination alone.

-73% of small cell carcinomas of the salivary gland
express cytokeratin 20 (Merkel cell subtype). These
cases demonstrate a longer overall survival than the
cytokeratin 20–negative group (pulmonary subtype).
- Both subtypes express neuroendocrine markers such as
chromogranin, synaptophysin, and CD56.

• Differential Diagnosis.
-Lymphoma (persistence of residual glandular structures
even in areas of extensive involvement)
-Solid-type adenoid cystic carcinoma (cribriform structures
are seen. Many tumor cells are positive for p63 or
calponin, and focal ductal structures show
immunoreactivity for CEA and EMA. Small cell carcinoma is
negative for these markers except EMA.
- metastatic cutaneous Merkel cell carcinoma (Clinical
history, examination, and clinical workup are essential )
• Large Cell Carcinoma
- Large cell carcinoma is a high-grade malignant tumor.
- Peak incidence is from the 7th-8th decade; no sex
preference is seen.

- Present with a rapidly growing firm mass with fixation to
adjacent tissues. Cervical lymphadenopathy at presentation is
common, most patients present in advanced stage (75% stage
IV).
- This is a highly aggressive neoplasm, with 2-year survival of
only 36%.
- Grossly, large cell carcinomas produce solid, tan-colored
infiltrative masses.
- Microscopic appearance:
 consist of sheets and irregular islands of large pleomorphic
cells with welldefined cell borders, copious amphophilic to
eosinophilic cytoplasm, and large nuclei containing prominent
nucleoli.
 Occasionally multinucleate tumor giant cells are present.
Mitoses, tumor necrosis, and lymphatic and vascular invasion
are common.
The stroma is desmoplastic and infiltrated by variable numbers
of lymphocytes and plasma cells.
 Interspersed reactive osteoclastic giant cells can also be
found.

• Large Cell Neuroendocrine Carcinoma:
-Demonstrates neuroendocrine features including rosette-
like structures and organoid growth with peripheral
palisading.
- The tumor cells express neuroendocrine markers such as
chromogranin and synaptophysin, but not CK20. Pan-
cytokeratin and EMA are also expressed.

• Lymphoepithelial Carcinoma :
-Rare , Usually in adults, with a mean age of 44.5
years, are affected, with no definite or slight female
predominance.
- Regional lymph node metastasis is seen in
approximately 40% of patients at presentation.
- Has the best prognosis among the undifferentiated
carcinomas.
- The infiltrative tumor grows in diffuse sheets,
anastomosing islands, nests, or cords, separated by
desmoplastic stroma.
-The tumor cells are typically large with eosinophilic
cytoplasm and indistinct cell borders.
-They possess vesicular nuclei and prominent nucleoli.

- The tumor cells are immunoreactive for cytokeratin and
EMA.
- Differential Diagnosis-
Nasopharyngeal undifferentiated carcinoma- histologically,
immunohistochemically, and ultrastructurally
indistinguishable.

• Primary salivary gland squamous cell carcinoma is a very
rare malignant tumor.
• Invasion from an adjacent squamous cell carcinoma or
metastasis should always be excluded.
• This entity is seldom diagnosed with confidence in the minor
salivary gland because it is not possible to rule out a
mucosal squamous cell carcinoma.
• This tumor mainly affects elderly men, with a mean age of
64 years. Prior radiation therapy have been implicated as
predisposing factors in some cases. Two thirds of tumors
occur in the parotid gland.
• Most patients present with a fast-growing, hard, fixed mass.
Regional lymph node involvement and facial nerve palsy are
common.

• The 5-year survival rate is only around 30%. Ulceration,
fixation, advanced patient age, advanced tumor stage,
and facial nerve palsy are unfavorable prognostic
factors.
• Grossly; most often an infiltrative, tan-colored lesion,
and hard.
-moderately to well-differentiated squamous cell
carcinoma consisting of sheets and islands of squamous
cells with readily identifiable keratin formation and
intercellular bridges. The stroma is desmoplastic.
• Differential Diagnosis
-High-grade mucoepidermoid carcinoma
-Metastatic carcinoma
-Warthin tumor, oncocytoma, and pleomorphic adenoma

• Very rare tumor, characterized by clusters of tumor
cells floating in large pools of extracellular mucin.
• Represents the histologic equivalent of mucinous or
colloid carcinoma of the gastrointestinal tract, breast,
and skin.
• All patients are adults, with slight male predilection.
• Tumor can recur or metastasize, but many patients
enjoy long survival.

• Low-grade malignant tumor characterized by mucin-containing
signet ring cells. It occurs almost exclusively in minor salivary
glands.
• Patients’ mean age is 56.4 years, with a female predilection of 2.5
: 1.
• The infiltrative tumor comprises narrow parallel strands, randomly
scattered small nests, or isolated cells.
• Signet ring cells are characterized by single or several cytoplasmic
mucin vacuoles and eccentric indented nuclei.
• Admixed with the signet ring cells are minor populations of tumor
cells with eosinophilic or clear cytoplasm. The overall cytologic
atypia is very mild with rare or absent mitoses and no necrosis.
• The tumor cells strongly express CAM5.2 (low molecular weight
cytokeratin) and p63, and variably actin, S100, and GFAP. Calponin
is negative.

Signet ring cell adenocarcinoma - single or several
cytoplasmic mucin vacuoles and eccentric indented
nuclei. admixed with the signet ring cells are minor
populations of tumor cells with eosinophilic or clear
cytoplasm.

• Adenocarcinoma NOS refers to primary carcinoma of the
salivary gland that exhibits glandular differentiation but
lacks diagnostic criteria of other defined tumor categories.
• Most commonly occurs in the elderly, the peak age being
between the 6th-8th decades, with a male predilection,
locations in descending order are parotid gland,
submandibular gland, palate, and buccal mucosa.
• The patients present with an asymptomatic or fast-
growing painful mass associated with ulceration and
fixation to the adjacent structures. Facial nerve palsy is
common.

• Grossly, the tumors show irregular infiltrative borders.
The cut surface is tan and solid, with areas of
hemorrhage or necrosis.
-Glandular or ductal structures with variable organization.
- The growth patterns are variable, including glandular,
papillary, cystic, cribriform, solid, lobular, nest, and
strand-like, with the single other specific neoplasms.
Unifying feature being the lack of recognizable patterns
diagnostic of other specific neoplasms.
-The neoplastic cells can be oncocytoid, clear, melanoma-
like, mucinous, sebaceous, or plasmacytoid.
-The glandular structures are mostly formed by one single
cell type (luminal cells only) .Infiltration of the normal
parenchyma, nerves, and blood vessels are common.

Adenocarcinoma not otherwise specified,1)intermediate grade,
growing in the form of large islands punctuated by occasional
glandular spaces. 2) Adenocarcinoma not otherwise specified,
comprising nondescript tubules lined by moderately atypical cells,
lacking diagnostic patterns of the various known tumor types.

• a/k/a embryoma, congenital carcinoma, or congenital basal
cell adenoma, is a tumor of newborns or infants that is
composed of primitive appearing cells with occasional ductal
formation, recapitulating embryonic salivary tissue.
• Occur in major salivary glands, most commonly in the
parotid.
• They present at birth or within the first or second year as an
asymptomatic mass.
- The majority of cells are primitive looking and basaloid and
possess large ovoid vesicular nuclei and a small amount of
cytoplasm.
- They form cellular ductules and solid organoid nests with
vague palisading of nuclei at the periphery of the tumor
islands.

- Mild nuclear atypia and variable mitotic activity are
present.
- Focally, ducts lined by larger polygonal to cuboidal cells
with eosinophilic cytoplasm can be identified, and the
ductal lumens often contain secretory product.
- Immunostaining for
cytokeratin highlights the
ductal structures. The
basaloid cells show
staining for S100 protein
and actin in the peripherally
located cells.

TUMORS OF SALIVARY GLANDS.pptx

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TUMORS OF SALIVARY GLANDS.pptx